PDBsum entry 1m46

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protein Protein-protein interface(s) links
Cell cycle protein PDB id
Protein chains
148 a.a. *
25 a.a. *
Waters ×81
* Residue conservation analysis
PDB id:
Name: Cell cycle protein
Title: Crystal structure of mlc1p bound to iq4 of myo2p, a class v myosin
Structure: Myosin light chain. Chain: a. Synonym: m1c1p. Engineered: yes. Iq4 motif from myo2p, a class v myosin. Chain: b. Synonym: iq4. Engineered: yes
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Gene: mlc1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: the peptide was chemically synthesized. The sequence of the peptide is naturally found in
Biol. unit: Tetramer (from PQS)
2.10Å     R-factor:   0.201     R-free:   0.239
Authors: M.Terrak,R.Dominguez
Key ref:
M.Terrak et al. (2003). Two distinct myosin light chain structures are induced by specific variations within the bound IQ motifs-functional implications. EMBO J, 22, 362-371. PubMed id: 12554638 DOI: 10.1093/emboj/cdg058
02-Jul-02     Release date:   27-Nov-02    
Go to PROCHECK summary

Protein chain
P53141  (MLC1_YEAST) -  Myosin light chain 1
149 a.a.
148 a.a.
Protein chain
Pfam   ArchSchema ?
P19524  (MYO2_YEAST) -  Myosin-2
1574 a.a.
25 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     vesicle   5 terms 
  Biological process     cell cycle   5 terms 
  Biochemical function     protein binding     6 terms  


DOI no: 10.1093/emboj/cdg058 EMBO J 22:362-371 (2003)
PubMed id: 12554638  
Two distinct myosin light chain structures are induced by specific variations within the bound IQ motifs-functional implications.
M.Terrak, G.Wu, W.F.Stafford, R.C.Lu, R.Dominguez.
IQ motifs are widespread in nature. Mlc1p is a calmodulin-like myosin light chain that binds to IQ motifs of a class V myosin, Myo2p, and an IQGAP-related protein, Iqg1p, playing a role in polarized growth and cytokinesis in Saccharomyces cerevisiae. The crystal structures of Mlc1p bound to IQ2 and IQ4 of Myo2p differ dramatically. When bound to IQ2, Mlc1p adopts a compact conformation in which both the N- and C-lobes interact with the IQ motif. However, in the complex with IQ4, the N-lobe no longer interacts with the IQ motif, resulting in an extended conformation of Mlc1p. The two light chain structures relate to two distinct subfamilies of IQ motifs, one of which does not interact with the N-lobes of calmodulin-like light chains. The correlation between light chain structure and IQ sequence is demonstrated further by sedimentation velocity analysis of complexes of Mlc1p with IQ motifs from Myo2p and Iqg1p. The resulting 'free' N-lobes of myosin light chains in the extended conformation could mediate the formation of ternary complexes during protein localization and/or partner recruitment.
  Selected figure(s)  
Figure 1.
Figure 1 Ribbon diagram of the structures of Mlc1p bound to IQ2 and IQ4 of Myo2p. (A) Compact structure of the Mlc1p -IQ2 complex. The N-lobe, the C-lobe and the IQ peptide are shown in blue, red and green, respectively (this color scheme is kept through all the figures). (B) Extended structure of the Mlc1p -IQ4 complex. (C) Superimposition of the structures of Mlc1p -IQ2 and Mlc1p -IQ4 (thinner trace). (D) Superimposition of the structures of Mlc1p -IQ2 with those of ELC -IQ complexes from scallop (yellow) and smooth muscle (pink) myosins (Xie et al., 1994; Houdusse and Cohen, 1996; Dominguez et al., 1998). Note how differences in the orientation of the N-lobes are mirrored by differences in the orientation of the C-terminal portions of the IQ motifs. (E) Superimposition of the extended structures of Mlc1p -IQ4 and scallop RLC -IQ (cyan) complexes. The myosin heavy chain fragment (yellow) bound to the scallop RLC is bent by 90. The Mg2+-bound (and fully open) N-lobe of the RLC binds to a conserved sequence (WQWWKLYSKVKPLL) of the myosin heavy chain that follows immediately after the 90 turn. Note that this N-lobe-specific target sequence does not make up part of a canonical IQ motif.
Figure 5.
Figure 5 IQ motif-binding interface of Mlc1p. (A) Compact conformation of the Mlc1p -IQ2 complex. The view is along the axis of the -helices of IQ2 (shown in green). The amino acids of Mlc1p are colored yellow, except for those amino acids that make direct contacts with the IQ peptide, which are depicted in red (the same amino acids are also colored red in Figure 3A). Two views are shown: on the left side of the figure, the IQ peptide has been moved out of its binding cleft manually to illustrate better the binding interface, while the view on the right side corresponds to the actual position of the IQ peptide in the crystal structure. (B) Extended structure of Mlc1p -IQ4 (same color scheme and orientation as A). Note how all of the amino acids of the N-lobe that interact with IQ2 in the compact structure become solvent exposed in this complex. The resulting surface would be available for interactions with a GxxxR-containing target without a need for the N-lobe to open.
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2003, 22, 362-371) copyright 2003.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19877718 D.J.Black, D.LaMartina, and A.Persechini (2009).
The IQ domains in neuromodulin and PEP19 represent two major functional classes.
  Biochemistry, 48, 11766-11772.  
18945678 G.Bajaj, Y.Zhang, M.I.Schimerlik, A.M.Hau, J.Yang, T.M.Filtz, C.Kioussi, and J.E.Ishmael (2009).
N-Methyl-D-aspartate Receptor Subunits Are Non-myosin Targets of Myosin Regulatory Light Chain.
  J Biol Chem, 284, 1252-1266.  
19183469 R.A.Veitia (2009).
On gene dosage balance in protein complexes: a comment on Semple JI, Vavouri T, Lehner B. A simple principle concerning the robustness of protein complex activity to changes in gene expression.
  BMC Syst Biol, 3, 16.  
18221262 E.C.Casavola, A.Catucci, P.Bielli, A.Di Pentima, G.Porcu, M.Pennestri, D.O.Cicero, and A.Ragnini-Wilson (2008).
Ypt32p and Mlc1p bind within the vesicle binding region of the class V myosin Myo2p globular tail domain.
  Mol Microbiol, 67, 1051-1066.  
18239852 K.M.Trybus (2008).
Myosin V from head to tail.
  Cell Mol Life Sci, 65, 1378-1389.  
18372636 M.B.Heintzelman, and M.J.Mateer (2008).
GpMyoF, a WD40 repeat-containing myosin associated with the myonemes of Gregarina polymorpha.
  J Parasitol, 94, 158-168.  
18164029 S.H.Lee, A.Weins, D.B.Hayes, M.R.Pollak, and R.Dominguez (2008).
Crystal structure of the actin-binding domain of alpha-actinin-4 Lys255Glu mutant implicated in focal segmental glomerulosclerosis.
  J Mol Biol, 376, 317-324.
PDB code: 2r0o
18587628 S.Pathmanathan, S.F.Elliott, S.McSwiggen, B.Greer, P.Harriott, G.B.Irvine, and D.J.Timson (2008).
IQ motif selectivity in human IQGAP1: binding of myosin essential light chain and S100B.
  Mol Cell Biochem, 318, 43-51.  
17628590 J.Bosch, S.Turley, C.M.Roach, T.M.Daly, L.W.Bergman, and W.G.Hol (2007).
The closed MTIP-myosin A-tail complex from the malaria parasite invasion machinery.
  J Mol Biol, 372, 77-88.
PDB code: 2qac
17208425 K.A.Taylor (2007).
Regulation and recycling of myosin V.
  Curr Opin Cell Biol, 19, 67-74.  
17562702 K.M.Trybus, M.I.Gushchin, H.Lui, L.Hazelwood, E.B.Krementsova, N.Volkmann, and D.Hanein (2007).
Effect of calcium on calmodulin bound to the IQ motifs of myosin V.
  J Biol Chem, 282, 23316-23325.  
17074768 M.Pennestri, S.Melino, G.M.Contessa, E.C.Casavola, M.Paci, A.Ragnini-Wilson, and D.O.Cicero (2007).
Structural basis for the interaction of the myosin light chain Mlc1p with the myosin V Myo2p IQ motifs.
  J Biol Chem, 282, 667-679.
PDB codes: 2fcd 2fce
17910470 S.Manceva, T.Lin, H.Pham, J.H.Lewis, Y.E.Goldman, and E.M.Ostap (2007).
Calcium regulation of calmodulin binding to and dissociation from the myo1c regulatory domain.
  Biochemistry, 46, 11718-11726.  
16568447 A.Ganoth, E.Nachliel, R.Friedman, and M.Gutman (2006).
Molecular dynamics study of a calmodulin-like protein with an IQ peptide: spontaneous refolding of the protein around the peptide.
  Proteins, 64, 133-146.  
16844751 A.Ganoth, R.Friedman, E.Nachliel, and M.Gutman (2006).
A molecular dynamics study and free energy analysis of complexes between the Mlc1p protein and two IQ motif peptides.
  Biophys J, 91, 2436-2450.  
16917818 J.D.Franke, A.L.Boury, N.J.Gerald, and D.P.Kiehart (2006).
Native nonmuscle myosin II stability and light chain binding in Drosophila melanogaster.
  Cell Motil Cytoskeleton, 63, 604-622.  
16625208 J.Liu, D.W.Taylor, E.B.Krementsova, K.M.Trybus, and K.A.Taylor (2006).
Three-dimensional structure of the myosin V inhibited state by cryoelectron tomography.
  Nature, 442, 208-211.
PDB code: 2dfs
16468996 P.Bielli, E.C.Casavola, A.Biroccio, A.Urbani, and A.Ragnini-Wilson (2006).
GTP drives myosin light chain 1 interaction with the class V myosin Myo2 IQ motifs via a Sec2 RabGEF-mediated pathway.
  Mol Microbiol, 59, 1576-1590.  
16415352 S.W.Crawley, la Roche, S.F.Lee, Z.Li, S.Chitayat, S.P.Smith, and G.P.Côté (2006).
Identification and characterization of an 8-kDa light chain associated with Dictyostelium discoideum MyoB, a class I myosin.
  J Biol Chem, 281, 6307-6315.  
16757473 X.D.Li, H.S.Jung, K.Mabuchi, R.Craig, and M.Ikebe (2006).
The globular tail domain of myosin Va functions as an inhibitor of the myosin Va motor.
  J Biol Chem, 281, 21789-21798.  
15792977 A.Vilfan (2005).
Elastic lever-arm model for myosin V.
  Biophys J, 88, 3792-3805.  
15853803 D.Köhler, S.Struchholz, and M.Bähler (2005).
The two IQ-motifs and Ca2+/calmodulin regulate the rat myosin 1d ATPase activity.
  FEBS J, 272, 2189-2197.  
16227209 J.E.Debreczeni, L.Farkas, V.Harmat, C.Hetényi, I.Hajdú, P.Závodszky, K.Kohama, and L.Nyitray (2005).
Structural evidence for non-canonical binding of Ca2+ to a canonical EF-hand of a conventional myosin.
  J Biol Chem, 280, 41458-41464.
PDB code: 2bl0
15746172 K.A.Young, and J.H.Caldwell (2005).
Modulation of skeletal and cardiac voltage-gated sodium channels by calmodulin.
  J Physiol, 565, 349-370.  
16120677 M.Terrak, G.Rebowski, R.C.Lu, Z.Grabarek, and R.Dominguez (2005).
Structure of the light chain-binding domain of myosin V.
  Proc Natl Acad Sci U S A, 102, 12718-12723.
PDB code: 1n2d
15929007 S.Melino, M.Pennestri, A.Santoprete, P.Bielli, M.Paci, A.Ragnini-Wilson, and D.O.Cicero (2005).
Assignment of the 1H, 13C and 15N resonances of Mlc1p from Saccharomices cerevisiae.
  J Biomol NMR, 31, 367-368.  
15037754 A.Bahloul, G.Chevreux, A.L.Wells, D.Martin, J.Nolt, Z.Yang, L.Q.Chen, N.Potier, A.Van Dorsselaer, S.Rosenfeld, A.Houdusse, and H.L.Sweeney (2004).
The unique insert in myosin VI is a structural calcium-calmodulin binding site.
  Proc Natl Acad Sci U S A, 101, 4787-4792.  
15037306 E.M.De La Cruz, and E.M.Ostap (2004).
Relating biochemistry and function in the myosin superfamily.
  Curr Opin Cell Biol, 16, 61-67.  
15210731 J.Luo, E.A.Vallen, C.Dravis, S.E.Tcheperegine, B.Drees, and E.Bi (2004).
Identification and functional analysis of the essential and regulatory light chains of the only type II myosin Myo1p in Saccharomyces cerevisiae.
  J Cell Biol, 165, 843-855.  
15504913 M.Lord, and T.D.Pollard (2004).
UCS protein Rng3p activates actin filament gliding by fission yeast myosin-II.
  J Cell Biol, 167, 315-325.  
12682054 C.A.Morris, A.L.Wells, Z.Yang, L.Q.Chen, C.V.Baldacchino, and H.L.Sweeney (2003).
Calcium functionally uncouples the heads of myosin VI.
  J Biol Chem, 278, 23324-23330.  
14504268 J.V.Kilmartin (2003).
Sfi1p has conserved centrin-binding sites and an essential function in budding yeast spindle pole body duplication.
  J Cell Biol, 162, 1211-1221.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.